The prevalence of spina bifida has decreased since folic acid fortification, but an estimated 800 pregnancies are affected each year in the US to women who ingested at least the recommended daily amount (400 micrograms) of folic acid. Because spina bifida is a serious condition that has substantial impacts on families and society, further strategies for prevention are warranted. Using data collected in a large US case-control study from years 1976 to the present, preventable risk factors for folic acid-resistant spina bifid will be identified. The Boston University Slone Epidemiology Center Birth Defects Study is a unique resource with detailed data on mothers of over 1100 spina bifida cases and 9000 controls on folic acid intakes. These data allow mothers to be classified according to sufficient o insufficient intake of folic acid during the periconceptional period. Further, detailed data are available on many other potential risk factors. In this project, we will explore whether maternal folic acid intake modifies associations between spina bifida risks and maternal early pregnancy antiepileptic use, antimicrobial use, and failed oral contraceptive use. In addition, we will exploe whether maternal folic acid intake, physical activity, diet quality, or inter-pregnancy interval modifies associations between spina bifida risk and maternal Hispanic ethnicity, indicators of low socioeconomic status, obesity, and early pregnancy fever. Further, patterns of folic acid intake among control women will be assessed, according to maternal occupational class and type and by parity and inter-pregnancy interval lengths, to identify target groups of women for interventions. Lastly, findings from National Birth Defects Prevention Study will be replicated with Slone Epidemiology Birth Defects Study data on maternal use of antihistamines, anti-nauseants, and non-steroidal anti-inflammatory drugs. Findings from this project will lead toward the ultimate goal of eliminating the occurrence of spina bifida.